Long Stoppage of Bisphosphonates Tied to More Fractures

40% higher risk in older women who went off osteoporosis meds for more than 2 years

by John Gever John Gever,Managing Editor, MedPage Today
November 05, 2017

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN DIEGO -- Older women taking bisphosphonate drugs for osteoporosis may want to be careful about stopping the drugs for long periods, as the risk of incurring bone fractures increases with the duration of the "drug holiday," a researcher said here.

Analysis of more than 150,000 female Medicare beneficiaries identified through records as "highly adherent, long-term bisphosphonate users" showed that those stopping treatment for more than 2 years were 40% more like to develop hip fractures (95% CI 20%-60%) after adjustment for potential confounders, compared with otherwise similar women who stayed on the medications, said Jeffrey Curtis, MD, of the University of Alabama at Birmingham.

Smaller but still statistically significant increases in hip fracture risk were apparent with shorter cessations of bisphosphonates, Curtis said during an oral presentation at the American College of Rheumatology annual meeting. A similar pattern was seen for wrist and distal forearm fractures, but the magnitudes were generally smaller and did not consistently reach statistical significance for durations of stoppage shorter than 2 years.

But Curtis stopped short of concluding that drug holidays should be avoided for older women on bisphosphonates. He noted that the absolute increase in fracture risk associated with stoppages of 2 years or more was rather modest, about one extra fracture per 100 patient-years compared with women staying on bisphosphonates.

He also pointed out that the drugs have risks of their own -- such as osteonecrosis of the jaw with long-term therapy -- that may be mitigated with holidays, and which were not addressed in the study.

As background for the study, Curtis cited warnings from the FDA and others about such risks, which has led to some recommendations that bisphosphonate therapy not be continuous and permanent in all osteoporosis patients. By the same token, though, the quantitative risks and benefits of drug stoppage have not been established, nor have the optimal holiday duration or the factors that may go into estimating it, he said.

To get at these issues, his group drew on Medicare data from 2006 to 2014, seeking to identify women on long-term therapy including those stopping it for defined intervals. The researchers focused on those on continuous, highly adherent (at least 80% of prescribed doses) therapy for at least 3 years, at which time up to 3 years of follow-up for fractures began. Patients were excluded or censored if they were taking other bone therapies.

Although the highest fracture rates were associated with this last duration category, hip fracture risk was nearly as high for stoppages lasting less than 3 months. Curtis speculated that this relatively high rate may stem from what he called the "sick stopper effect" -- people going off their medications because of other health issues. He argued that this effect is likely to be most prominent for short periods of cessation and that those last more than 2 years probably reflect a decision to end bisphosphonates for reasons related to the drugs.

He conceded, though, that the Medicare data did not include specific reasons for stopping bisphosphonate therapy. Other limitations included the reliance on administrative data and the 3-year limit on follow-up. Curtis said it would be useful to study effects of even longer cessations in bisphosphonate therapy.

Women included in the analysis were mostly elderly (two-thirds older than 75); 4.2% had a history of fractures prior to inclusion the study. Some 27% had Charlson comorbidity score of 1 or 2 and 29% had scores of 3 or more. Approximately 3,600 women incurred hip fractures during follow-up; there were about 2,000 wrist and distal forearm fractures.

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